Source Paper
PS2APP Transgenic Mice, Coexpressing hPS2mut and hAPPswe, Show Age-Related Cognitive Deficits Associated with Discrete Brain Amyloid Deposition and Inflammation
J. Grayson Richards, Guy A. Higgins, Abdel-Mouttalib Ouagazzal, Laurence Ozmen, James N. C. Kew et al.
Journal of Neuroscience • 2003
Behavioral Testing
Objective: Assessment of age-related cognitive deficits in PS2APP transgenic mice at multiple time points (4, 8, 12, and 16 months) and investigation of changes in behavior, electrophysiology, amyloid-beta load, histopathology, and immunoelectron microscopy
Protocol Steps
Behavioral Testing
Conduct behavioral assessment of PS2APP transgenic mice at each age cohort
Note: Testing performed at 4, 8, 12, and 16 months of age
View evidence from paper
“Each age cohort was investigated for changes in behavior, electrophysiology of synapse efficacy, ELISA-determined Aβ load, histopathology, and in immunoelectron microscopy”
Electrophysiology Assessment
Measure synapse efficacy and electrophysiological parameters including dentate gyrus post-tetanic potentiation and paired-pulse parameters
Note: Dentate gyrus post-tetanic potentiation was significantly attenuated at 17 months
View evidence from paper
“Dentate gyrus post-tetanic potentiation was significantly attenuated at 17 months, and there were also significant differences in paired-pulse parameters”
ELISA Analysis for Aβ Load
Determine amyloid-beta load using ELISA methodology, measuring Aβ 1-40 and Aβ 1-42 levels
Note: As early as 5 months, increased levels of insoluble Aβ were detected with Aβ 1-40 levels exceeding those of Aβ 1-42
View evidence from paper
“ELISA-determined Aβ load, histopathology, and in immunoelectron microscopy. At the same age, increased levels of insoluble Aβ were detected by ELISA, with Aβ 1-40 levels exceeding those of Aβ 1-42”
Histopathological Analysis
Perform histopathological examination to assess amyloid deposition and inflammation in brain regions
Note: Cognitive deficits first observed at 8 months when Aβ deposits and inflammation were restricted to discrete brain regions (subiculum and frontolateral cortex)
View evidence from paper
“Cognitive deficits were first observed at 8 months when Aβ deposits and inflammation were restricted to discrete brain regions, namely the subiculum and frontolateral (motor and orbital) cortex”
Immunoelectron Microscopy
Perform immunoelectron microscopy to visualize pre-plaque, immunogold-labeled extracellular fibrillar Aβ
Note: As early as 5 months, electron microscopy revealed presence of pre-plaque, immunogold-labeled extracellular fibrillar Aβ in discrete brain regions
View evidence from paper
“As early as 5 months, electron microscopy revealed the presence, in these regions, of pre-plaque, immunogold-labeled extracellular fibrillar Aβ”